Efficacy and Safety of Lixisenatide Versus Placebo on Top of Basal Insulin and/or Oral Antidiabetic Treatment in Older Type 2 Diabetic Patients

NCT01798706 | Completed Phase 3 Results DMC

• 3 other identifiers: EFC127032012-003292-19U1111-1132-9156
• Study Type: interventional
• Target: 350
• Locations: 13 countries
• Sites: 83

Brief Summary

Primary objective: \- To evaluate the effect of lixisenatide versus placebo over a period of 24 weeks on glycemic control, as evaluated by glycosylated hemoglobin (HbA1c) reduction, in older type 2 diabetes participants (T2DM) who are inadequately controlled with their current anti-diabetic treatment regimen. Main secondary objective: \- To assess the safety and tolerability of lixisenatide compared to placebo in older T2DM participants (including occurrence of documented (Plasma Glucose PG \< 60 mg/dL) symptomatic hypoglycemia and gastrointestinal side effects). Other secondary objectives:

• To assess the effect of lixisenatide compared to placebo after 24-week treatment on:
• Fasting plasma glucose (FPG);
• During liquid standardized breakfast meal challenge test : 2 hour- Postprandial Plasma Glucose (PPG) and Plasma Glucose Excursion;
• 7-point Self-monitored plasma glucose (SMPG) profile;
• Body weight;
• Change in total daily dose of basal insulin (if taken);
• Percentage of participants requiring rescue therapy
• Safety and tolerability;
• To assess lixisenatide pharmacokinetic profile;
• To assess anti-lixisenatide antibody development.

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Absolute Change in HbA1c From Baseline to Week 24

  Change in HbA1c was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using last on-treatment observation carried forward (LOCF). On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. Here, number of participants analyzed=participants with baseline and at least one post-baseline HbA1c assessment during on-treatment period.

  Baseline, Week 24

Secondary Outcomes (10)

• Change in 2-Hour PPG From Baseline to Week 24

  Baseline, Week 24

• Change in Average 7-point SMPG Profiles From Baseline to Week 24

  Baseline, Week 24

• Change in Body Weight From Baseline to Week 24

  Baseline, Week 24

• Change in FPG From Baseline to Week 24

  Baseline, Week 24

• Percentage of Participants Requiring Rescue Therapy During 24 Week Treatment Period

  Baseline up to Week 24

Study Arms (2)

Lixisenatide

EXPERIMENTAL

Lixisenatide 10 mcg once daily (QD) for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24. If the maintenance dose of 20 mcg was not tolerated, dose could be reduced to 10 mcg.

Drug: Lixisenatide (AVE0010); Drug: Antidiabetic background therapy

Placebo

PLACEBO COMPARATOR

Placebo (matched to lixisenatide) QD for 24 Weeks.

Drug: Placebo; Drug: Antidiabetic background therapy

Interventions

Lixisenatide (AVE0010) DRUG

Pharmaceutical form: Solution for injection in pre-filled pen administered 30 to 60 minutes before breakfast in the morning Route of administration: Subcutaneous injection

Also known as: Lyxumia

Lixisenatide

Placebo DRUG

Pharmaceutical form: Solution for injection in pre-filled pen administered 30 to 60 minutes before breakfast in the morning Route of administration: Subcutaneous injection

Placebo

Antidiabetic background therapy DRUG

Participants received a stable regimen of anti-diabetic background therapy for at least 3 months prior to screening, during the placebo run-in period and the 24 week treatment period. Allowed background antidiabetic therapy included metformin, sulfonylurea (except glibenclamide \>10 mg, gliclazide \>160 mg), meglitinides (except repaglinide \>6 mg), pioglitazone and basal insulin. Insulin glargine, neutral protamine hagedorn (NPH) insulin, detemir, lente and ultralente were considered as basal insulin.

Lixisenatide; Placebo

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Older participants, aged 70 years and above, with T2DM inadequately controlled on their current anti-diabetic pharmaceutical treatment regimen.
• Signed written informed consent.

You may not qualify if:

• At screening HbA1c ≤7.0% or \>10% (Acknowledging that the threshold of 7% may not be appropriate for all older participants and that this was the responsibility of the investigator to include the participant based on an individual evaluation of the expected benefits of better glycemic control versus risk of hypoglycemia).
• At screening participants on both basal insulin and sulfonylurea or basal insulin and meglitinides.
• At screening FPG \>250 mg/dL (\>13.9 mmol/L).
• Type 1 diabetes mellitus or history of ketoacidosis within one year prior to the screening visit.
• Type 2 diabetes mellitus diagnosed less than 1 year prior to screening.
• Anti-diabetic treatment not at a stable regimen or initiated within the last 3 months prior to screening.
• Treatment within the 3 months preceding the screening with other anti-diabetic agent than allowed background therapy. Allowed therapy includes metformin, sulfonylurea (except glibenclamide \>10mg, gliclazide \>160mg), meglitinides (except repaglinide \>6mg), pioglitazone and basal insulin and should follow local product circulars and labeling restrictions for the study population.
• Participants who had been on an approved or an investigational Glucagon-like peptide 1 (GLP-1) medication (exenatide, liraglutide, lixisenatide or others).
• History of severe hypoglycemia associated with symptoms unawareness or results in unconsciousness/coma/seizure in the 6 months prior to screening.
• BMI \<22 or \>40 kg/m\^2.
• Malnutrition assessed clinically by the investigator or any sub-investigator and by Mini-Nutritional Assessment-Short Form (MNA-SF) score \<12 in countries (the judgment of the investigator prevails on questionnaires scores).
• Cognitive disorder and dementia assessed clinically by the investigator or any sub investigator and by Mini Mental State Examination (MMSE) score \<24 (the judgment of the investigator prevails on questionnaires scores), or any neurologic disorder that affected the participant's ability to participate in the study.
• Participant who had a glomerular filtration rate (eGFR) (using the Modification of Diet in Renal Disease (MDRD) formula \<30ml/min/1.73m\^2).
• Participant with severe or uncontrolled disease, or any clinically significant abnormality identified on physical examination or investigational clinical procedure that, in the judgment of the investigator or any sub-investigator, would preclude safe completion of the study or constrains efficacy assessment.
• Laboratory findings at the time of screening:

Sponsors & Collaborators

• Sanofi: lead

Study Sites (83)

Investigational Site Number 840010

La Jolla, California, 92037, United States

Location

Investigational Site Number 840015

Norwalk, California, 90650, United States

Location

Investigational Site Number 840003

Miami, Florida, 33156, United States

Location

Investigational Site Number 840012

Miami, Florida, 33156, United States

Location

Investigational Site Number 840002

Des Moines, Iowa, 50314, United States

Location

Investigational Site Number 840008

Oxon Hill, Maryland, 20745, United States

Location

Investigational Site Number 840004

Rockville, Maryland, 20852, United States

Location

Investigational Site Number 840017

Biloxi, Mississippi, 39531, United States

Location

Investigational Site Number 840009

Omaha, Nebraska, 68131, United States

Location

Investigational Site Number 840016

Salisbury, North Carolina, 28144, United States

Location

Investigational Site Number 840006

Fargo, North Dakota, 58103, United States

Location

Investigational Site Number 840014

Canal Fulton, Ohio, 44614, United States

Location

Investigational Site Number 840011

St. George, Utah, 84790, United States

Location

Investigational Site Number 840007

Milwaukee, Wisconsin, 53209, United States

Location

Investigational Site Number 036002

Box Hill, 3128, Australia

Location

Investigational Site Number 036006

Brookvale, 2100, Australia

Location

Investigational Site Number 036004

Camperdown, 2050, Australia

Location

Investigational Site Number 036005

Gosford, 2250, Australia

Location

Investigational Site Number 036001

Heidelberg, 3081, Australia

Location

Investigational Site Number 036003

Parkville, 3050, Australia

Location

Investigational Site Number 100002

Plovdiv, 4002, Bulgaria

Location

Investigational Site Number 100005

Plovdiv, 4002, Bulgaria

Location

Investigational Site Number 100003

Sofia, 1632, Bulgaria

Location

Investigational Site Number 100004

Stara Zagora, 6000, Bulgaria

Location

Investigational Site Number 100001

Varna, 9000, Bulgaria

Location

Investigational Site Number 124003

Hamilton, L8L 5G8, Canada

Location

Investigational Site Number 124007

London, N6B 2E3, Canada

Location

Investigational Site Number 124001

Saint Romuald, G6W 5M6, Canada

Location

Investigational Site Number 124002

Sherbrooke, J1H 5N4, Canada

Location

Investigational Site Number 124005

Vancouver, V5Z 1M9, Canada

Location

Investigational Site Number 124006

Vancouver, V5Z 1M9, Canada

Location

Investigational Site Number 124008

Westmount, H3Z 1E5, Canada

Location

Investigational Site Number 124004

Winnipeg, R3E 3P4, Canada

Location

Investigational Site Number 208005

Esbjerg, 6700, Denmark

Location

Investigational Site Number 208001

København NV, 2400, Denmark

Location

Investigational Site Number 208004

København S, 2300, Denmark

Location

Investigational Site Number 208002

Slagelse, 4200, Denmark

Location

Investigational Site Number 208003

Svendborg, 5700, Denmark

Location

Investigational Site Number 276005

Dresden, 01307, Germany

Location

Investigational Site Number 276004

Essen, 45359, Germany

Location

Investigational Site Number 276002

München, 80639, Germany

Location

Investigational Site Number 276001

Münster, 48145, Germany

Location

Investigational Site Number 276006

Pirna, 01796, Germany

Location

Investigational Site Number 276007

Pohlheim, 35415, Germany

Location

Investigational Site Number 276008

Potsdam, 14469, Germany

Location

Investigational Site Number 276003

Saarlouis, 66740, Germany

Location

Investigational Site Number 578001

Hønefoss, 3515, Norway

Location

Investigational Site Number 578005

Kongsvinger, 2212, Norway

Location

Investigational Site Number 578003

Oslo, Norway

Location

Investigational Site Number 578006

Stavanger, 4095, Norway

Location

Investigational Site Number 578004

Trondheim, 7012, Norway

Location

Investigational Site Number 604001

Arequipa, Peru

Location

Investigational Site Number 604011

Lima, 27, Peru

Location

Investigational Site Number 604005

Lima, LIMA 10, Peru

Location

Investigational Site Number 604003

Lima, LIMA 14, Peru

Location

Investigational Site Number 604006

Lima, LIMA 31, Peru

Location

Investigational Site Number 604002

Lima, Peru

Location

Investigational Site Number 604007

Lima, Peru

Location

Investigational Site Number 604008

Piura, Peru

Location

Investigational Site Number 616004

Gdansk, 80-858, Poland

Location

Investigational Site Number 616003

Krakow, 31-024, Poland

Location

Investigational Site Number 616001

Poznan, 61-665, Poland

Location

Investigational Site Number 616002

Ruda Śląska, 41-709, Poland

Location

Investigational Site Number 616006

Szczecin, 70-506, Poland

Location

Investigational Site Number 710003

Cape Town, 7500, South Africa

Location

Investigational Site Number 710002

Cape Town, 7530, South Africa

Location

Investigational Site Number 710004

Somerset West, 7130, South Africa

Location

Investigational Site Number 724001

Alzira, 46600, Spain

Location

Investigational Site Number 724005

Barcelona, 08035, Spain

Location

Investigational Site Number 724006

Hostalets de Balenyà, 08550, Spain

Location

Investigational Site Number 724003

Madrid, 28046, Spain

Location

Investigational Site Number 724002

Sanlúcar de Barrameda, 11540, Spain

Location

Investigational Site Number 724004

Santiago de Compostela, 15706, Spain

Location

Investigational Site Number 752006

Gothenburg, 405 45, Sweden

Location

Investigational Site Number 752007

Härnösand, 871 82, Sweden

Location

Investigational Site Number 752002

Lund, 22221, Sweden

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Investigational Site Number 752004

Malmo, 211 52, Sweden

Location

Investigational Site Number 752003

Stockholm, 111 57, Sweden

Location

Investigational Site Number 752001

Stockholm, 171 76, Sweden

Location

Investigational Site Number 826003

Bexhill-on-Sea, TN39 4SP, United Kingdom

Location

Investigational Site Number 826001

Glasgow, United Kingdom

Location

Investigational Site Number 826002

Irvine, KA12 0AY, United Kingdom

Location

Investigational Site Number 826004

Trowbridge, BA14 8QA, United Kingdom

Location

Related Publications (2)

• Meneilly GS, Roy-Duval C, Alawi H, Dailey G, Bellido D, Trescoli C, Manrique Hurtado H, Guo H, Pilorget V, Perfetti R, Simpson H; GetGoal-O Trial Investigators. Lixisenatide Therapy in Older Patients With Type 2 Diabetes Inadequately Controlled on Their Current Antidiabetic Treatment: The GetGoal-O Randomized Trial. Diabetes Care. 2017 Apr;40(4):485-493. doi: 10.2337/dc16-2143. Epub 2017 Feb 10.

  PMID: 28188240 RESULT

• Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.

  PMID: 39963952 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

lixisenatide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2013
• First Posted: February 26, 2013
• Study Start: June 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: April 18, 2017
• Results First Posted: October 14, 2016

Record last verified: 2017-03

Locations

NO (5); DE (8); SE (6); ZA (3); DK (5); PL (5); PE (8); AU (6); US (14); ES (6); GB (4); BU (5); CA (8)